Closed-loop Artificial Pancreas: Algorithm Engineering and Clinical Evaluation

描述（由申请人提供）：本提案旨在建立一个有前途的研究路线，该研究已经产生了闭环人工胰腺（AP）的工作原型，该原型结合了连续葡萄糖传感和通过控制算法自动胰岛素输送。AP由三部分组成：连续式葡萄糖传感器、连续式皮下胰岛素输注泵和人工胰腺软件（APS）。APS正处于食品和药物管理局用于全自动闭环控制临床试验的最后审查阶段（主文件MAF-1625）。具体目标是：1)人工胰腺的发展，以优化胰岛素输送，最大限度地减少与膳食相关的葡萄糖偏差；2)人工胰腺的扩展，以包括胰岛素敏感性的改变和个体差异；3)使用多参数模型预测控制（mpMPC）的算法的进一步发展，以减少在线计算，制定有效的在线监测策略，以确保AP正常运行。并适应多种输入系统。为了实现我们的胰岛素输送全自动闭环装置的总体目标，我们将采用分阶段的方法，其中临床研究也有并行的工程设计方法，以完善我们的AP。将使用硅测试和人体临床测试来验证模型开发的每个步骤。这条研究路线的最终目标是一种功能性AP，它将通过控制胰岛素输送来响应检测到的葡萄糖水平变化模式，提供全天候的葡萄糖调节，以实现1型糖尿病患者的最佳葡萄糖调节。在为后续胰岛素输送设定限制时，将特别考虑先前输注的潜在可用胰岛素量（胰岛素-机载）。该提案描述了血糖调节的多参数模型预测控制方法，并在夜间、用餐和运动条件下对AP进行了广泛的计算机和临床验证。这个应用程序源于加州大学圣巴巴拉分校（UCSB）的系统工程师和位于不到10英里远的著名的Sansum糖尿病研究所（Sansum）的专门从事糖尿病研究的研究医生之间的长期合作。该团队在人工胰腺文献和糖尿病技术的国际领先地位方面做出了重大贡献。

DESCRIPTION (provided by applicant): This proposal seeks to build on a promising line of research that has already resulted in a working prototype of a closed-loop artificial pancreas (AP) that combines continuous glucose sensing with automated insulin delivery via a control algorithm. The AP consists of three components: a continuous glucose sensor, a continuous subcutaneous insulin infusion pump, and artificial pancreas software (APS). The APS is in the final stages of review by the Food and Drug Administration for use in fully automated closed-loop control clinical trials (Master File MAF-1625 ). The specific aims are: 1) Development of the Artificial Pancreas to optimize insulin delivery and minimize meal-related excursions in glucose, 2) Expansion of the Artificial Pancreas to include alterations and individual differences in insulin sensitivity, and 3) Further development of the algorithms using multi-parametric model predictive control (mpMPC) in order to reduce online computation, develop effective online monitoring strategies to ensure that the AP is operating properly, and accommodate multiple input systems. In the quest to achieve our overall goal of a completely automated closed-loop device for insulin delivery, we will utilize a staged approach in which the clinical studies also have a concurrent engineering design approach in order to refine our AP. In silico testing and human in-clinic testing will be used to validate each step of model development. The ultimate goal of this line of research is a functional AP that will provide around-the-clock glucose regulation through controlled insulin delivery in response to detected patterns of changes in glucose levels in order to achieve optimal glucose regulation in subjects with type 1 diabetes. Special consideration will be given to the amount of potentially available insulin from prior infusions (insulin-on-board) in setting constraints for subsequent insulin delivery. The proposal describes multi-parametric model predictive control approaches to glycemic regulation and extensive in silico and clinical validation of the AP under overnight, meal, and exercise conditions. This application grows out of a long-standing collaboration between systems engineers at the University of California, Santa Barbara (UCSB) and research physicians specializing in diabetes research at the prestigious Sansum Diabetes Research Institute (Sansum) located less than ten miles away. This team has distinguished itself as a major contributor to the artificial pancreas literature and as an international leader in diabetes technology. PUBLIC HEALTH RELEVANCE: This project aims to develop a functional artificial pancreas that will provide around-the-clock glucose regulation through controlled insulin delivery in response to detected patterns of changes in glucose levels in order to achieve optimal glucose regulation in subjects with type 1 diabetes. Special consideration will be given to the amount of potentially available insulin from prior infusions (insulin-on-board) in setting constraints for subsequent insulin delivery. The proposal describes multi-parametric model predictive control approaches to glycemic regulation and extensive in silico and clinical validation of the AP under overnight, meal, and exercise conditions.